Susceptibility of Escherichia coli to L-selenaproline and other L-proline analogues in laboratory culture media and normal human urine

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The aims of this study were to identify analogues of L-proline which inhibit the growth of Escherichia coli in both laboratory culture media and normal human urine and to study their mechanisms of uptake. The susceptibility of E. coli to L-proline analogues was studied by radial streak assays on agar plates and by minimal inhibitory concentration determinations in liquid media. Only L-selenaproline (SCA) inhibited growth in Mueller-Hinton medium and human urine as well as in glucose minimal medium. L-Proline did not prevent the inhibition of growth by SCA and strains defective in L-proline transport were as susceptible to SCA as wild-type strains. However, E. coli was resistant to SCA in the presence of L-cysteine and L-cystine. Spontaneous mutants selected for resistance to SCA or L-selenocystine were resistant to the other compound and had reduced growth in minimal medium containing L-cysteine or L-cystine as the sole sulfur source. L-selenaproline inhibited the growth of E. coli under conditions that may occur in the urinary tract and appeared to be taken up by the L-cystine transport system. Although urinary tract infections caused by E. coli can be treated with sulfamethoxazole/trimethoprim and quinolones, resistance to these antibiotics has been increasing. These results suggest that L-selenaproline may represent a new class of compounds that could be used to treat these infections.